The Stabilization of Amorphous Zopiclone in an Amorphous Solid Dispersion

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Solid-State Chemistry

Background:

• Zopiclone is a psychotherapeutic agent with poor aqueous solubility, limiting its bioavailability.
• Amorphous forms of drugs can offer improved solubility and dissolution rates compared to crystalline forms.
• Developing stable amorphous solid dispersions is crucial for enhancing the performance of poorly soluble drugs.

Purpose of the Study:

• To prepare and characterize an amorphous form of zopiclone.
• To develop and characterize a stable amorphous solid dispersion of zopiclone with polyvinylpyrrolidone-25 (PVP-25).
• To evaluate the physico-chemical properties, stability, solubility, and dissolution performance of amorphous zopiclone and its solid dispersion.

Main Methods:

• Amorphous zopiclone prepared via melt quench-cooling.
• Amorphous solid dispersion prepared using solvent evaporation (zopiclone, PVP-25, methanol) followed by freeze-drying.
• Characterization using DSC, FT-IR, TGA, SEM, HSM, XRD, solubility, and dissolution studies.

Main Results:

• Amorphous zopiclone was identified as a fragile glass, susceptible to moisture and temperature.
• Exposure to moisture rapidly converted amorphous zopiclone to its crystalline dihydrated form.
• The zopiclone-PVP-25 amorphous solid dispersion exhibited enhanced aqueous solubility and improved stability compared to amorphous zopiclone.

Conclusions:

• The stability of amorphous zopiclone is significantly affected by temperature and water.
• Amorphous solid dispersion technology offers a viable strategy to improve the solubility and stability of zopiclone.
• The developed amorphous solid dispersion demonstrates potential for enhanced therapeutic efficacy of zopiclone.